Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D

Background Desmin-related myopathy (DRM) is an autosomally inherited skeletal and cardiac myopathy, mainly caused by dominant mutations in the desmin gene (DES).We describe new families carrying the p.S13F or p.N342D DES mutations, the cardiac phenotype of all carriers, and the founder effects. Methods We collected the clinical details of all carriers of p. S13F or p.N342D. The founder effects were studied using genealogy and haplotype analysis. Results We identified three new index patients carrying the p.S13F mutation and two new families carrying the p.N342D mutation. In total, we summarised the clinical details of 39 p. S13F carriers (eight index patients) and of 21 p.N342D carriers (three index patients). The cardiac phenotype of p.S13F carriers is fully penetrant and severe, characterised by cardiac conduction disease and cardiomyopathy, often with right ventricular involvement. Although muscle weakness is a prominent and presenting symptom in p.N342D carriers, their cardiac phenotype is similar to that of p.S13F carriers. The founder effects of p.S13F and p.N342D were demonstrated by genealogy and haplotype analysis. Conclusion DRM may occur as an apparently isolated cardiological disorder. The cardiac phenotypes of the DES founder mutations p.S13F and p.N342D are characterised by cardiac conduction disease and cardiomyopathy, often with right ventricular involvement

Model Adaptation with Synthetic and Real Data for Semantic Dense Foggy Scene Understanding

This work addresses the problem of semantic scene understanding under dense fog. Although considerable progress has been made in semantic scene understanding, it is mainly related to clear-weather scenes. Extending recognition methods to adverse weather conditions such as fog is crucial for outdoor applications. In this paper, we propose a novel method, named Curriculum Model Adaptation (CMAda), which gradually adapts a semantic segmentation model from light synthetic fog to dense real fog in multiple steps, using both synthetic and real foggy data. In addition, we present three other main stand-alone contributions: 1) a novel method to add synthetic fog to real, clear-weather scenes using semantic input; 2) a new fog density estimator; 3) the Foggy Zurich dataset comprising $3808$ real foggy images, with pixel-level semantic annotations for $16$ images with dense fog. Our experiments show that 1) our fog simulation slightly outperforms a state-of-the-art competing simulation with respect to the task of semantic foggy scene understanding (SFSU); 2) CMAda improves the performance of state-of-the-art models for SFSU significantly by leveraging unlabeled real foggy data. The datasets and code are publicly available.Comment: final version, ECCV 201

M-theory moduli spaces and torsion-free structures

Motivated by the description of $\mathcal{N}=1$ M-theory compactifications to four-dimensions given by Exceptional Generalized Geometry, we propose a way to geometrize the M-theory fluxes by appropriately relating the compactification space to a higher-dimensional manifold equipped with a torsion-free structure. As a non-trivial example of this proposal, we construct a bijection from the set of $Spin(7)$-structures on an eight-dimensional $S^{1}$-bundle to the set of $G_{2}$-structures on the base space, fully characterizing the $G_{2}$-torsion clases when the total space is equipped with a torsion-free $Spin(7)$-structure. Finally, we elaborate on how the higher-dimensional manifold and its moduli space of torsion-free structures can be used to obtain information about the moduli space of M-theory compactifications.Comment: 24 pages. Typos fixed. Minor clarifications adde

Effects of testicular microlithiasis on Doppler parameters: report of three cases

BACKGROUND: Testicular microlithiasis is a rare, usually asymptomatic, non-progressive disease of the testes associated with various genetic anomalies, infertility and testicular tumors. According to our literature search, there is no specific data about Doppler findings in this disease. CASE PRESENTATION: Doppler findings of three cases of testicular microlithiasis during last two years in our institution are presented. CONCLUSIONS: Although our hypothesis was to find increased Doppler parameters due to intratesticular arterial compression, our findings suggest that there are no Doppler findings specific to testicular microlithiasis

Eliminating the mystery from the concept of emergence

While some branches of complexity theory are advancing rapidly, the same cannot be said for our understanding of emergence. Despite a complete knowledge of the rules underlying the interactions between the parts of many systems, we are often baffled by their sudden transitions from simple to complex. Here I propose a solution to this conceptual problem. Given that emergence is often the result of many interactions occurring simultaneously in time and space, an ability to intuitively grasp it would require the ability to consciously think in parallel. A simple exercise is used to demonstrate that we do not possess this ability. Our surprise at the behaviour of cellular automata models, and the natural cases of pattern formation they mimic, is then explained from this perspective. This work suggests that the cognitive limitations of the mind can be as significant a barrier to scientific progress as the limitations of our senses

The Involvement of IL-17A in the Murine Response to Sub-Lethal Inhalational Infection with Francisella tularensis

Background: Francisella tularensis is an intercellular bacterium often causing fatal disease when inhaled. Previous reports have underlined the role of cell-mediated immunity and IFNc in the host response to Francisella tularensis infection. Methodology/Principal Findings: Here we provide evidence for the involvement of IL-17A in host defense to inhalational tularemia, using a mouse model of intranasal infection with the Live Vaccine Strain (LVS). We demonstrate the kinetics of IL-17A production in lavage fluids of infected lungs and identify the IL-17A-producing lymphocytes as pulmonary cd and Th17 cells. The peak of IL-17A production appears early during sub-lethal infection, it precedes the peak of immune activation and the nadir of the disease, and then subsides subsequently. Exogenous airway administration of IL-17A or of IL-23 had a limited yet consistent effect of delaying the onset of death from a lethal dose of LVS, implying that IL-17A may be involved in restraining the infection. The protective role for IL-17A was directly demonstrated by in vivo neutralization of IL-17A. Administration of anti IL-17A antibodies concomitantly to a sub-lethal airway infection with 0.16LD50 resulted in a fatal disease. Conclusion: In summary, these data characterize the involvement and underline the protective key role of the IL-17A axis in the lungs from inhalational tularemia

Investigation of attentional bias in obsessive compulsive disorder with and without depression in visual search

Copyright: © 2013 Morein-Zamir et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedWhether Obsessive Compulsive Disorder (OCD) is associated with an increased attentional bias to emotive stimuli remains controversial. Additionally, it is unclear whether comorbid depression modulates abnormal emotional processing in OCD. This study examined attentional bias to OC-relevant scenes using a visual search task. Controls, non-depressed and depressed OCD patients searched for their personally selected positive images amongst their negative distractors, and vice versa. Whilst the OCD groups were slower than healthy individuals in rating the images, there were no group differences in the magnitude of negative bias to concern-related scenes. A second experiment employing a common set of images replicated the results on an additional sample of OCD patients. Although there was a larger bias to negative OC-related images without pre-exposure overall, no group differences in attentional bias were observed. However, OCD patients subsequently rated the images more slowly and more negatively, again suggesting post-attentional processing abnormalities. The results argue against a robust attentional bias in OCD patients, regardless of their depression status and speak to generalized difficulties disengaging from negative valence stimuli. Rather, post-attentional processing abnormalities may account for differences in emotional processing in OCD.Peer reviewedFinal Published versio

Reconstructing the three-dimensional GABAergic microcircuit of the striatum

A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100 mu m of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are interconnected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study